Sexual malformations occur in congenital adrenal cortical hyperplasia, a disease of man, due to an autosomal recessive defect in any one of several steroidogenic enzymes. By the use of specific inhibitors of these enzymes and antibodies for testosterone we have produced animal models of these human genetic defects. With a similar use of recently prepared antibodies specific for rat LH and FSH, we plan to determine whether these hormones are involved in the pathogenesis of genetic defects of sexual differentiation. We propose to pursue our studies of the mechanism of congenital and postnatal sexual malformations occurring in congenital adrenal hyperplasia and in the sex-linked defect of male rat pseudohermaphroditism which resembles the human sex-linked defect of testicular feminization. The pseudohermaphrodite has a female pattern of adrenal, liver and testicular sterodogenesis and of functioning of the hypothalamic sexual center as a result of defects in the "organizing" or "imprinting" action of testosterone. We plan to develop the use of newly discovered site-specific inhibitors of C17-20 lyase and testosterone 5 alpha-reductase to make animal models of defects in these enzyme systems. We plan to extend the use of the unique, highly specific tools developed in our laboratory (stoichiometric inhibitors, testosterone-antibodies, antiandrogens) to investigate malformations of the controls of the onset of puberty, adult reproductive capacity, and of "imprinting" of masculine or feminine patterns of adult liver adrenal and testicular hypothalamic sexual center functioning.